[Case of peripartum cardiomyopathy misdiagnosed as pulmonary changes due to COVID-19].

A 37-year-old female patient was admitted 16 days after delivery in a hospital for infectious diseases with cough, shortness of breath, and infiltrative changes in the lungs that were interpreted as viral pneumonia. Considering the failure of therapy and the history, peripartum cardiomyopathy was suspected. Examination revealed a decrease in left ventricular ejection fraction to 30 %, ultrasonic signs of lung congestion and bilateral hydrothorax. The patient was diagnosed with peripartum cardiomyopathy accompanied by functional class 4 heart failure. A specific feature of this case was fast positive dynamics with complete regression of the clinical picture of congestion and improvement of the left ventricular myocardial function associated with the treatment.

Further delineation of a rare recessive encephalomyopathy linked to mutations in GFER thanks to data sharing of whole exome sequencing data.

BACKGROUND: Alterations in GFER gene have been associated with progressive mitochondrial myopathy, congenital cataracts, hearing loss, developmental delay, lactic acidosis and respiratory chain deficiency in 3 siblings born to consanguineous Moroccan parents by homozygosity mapping and candidate gene approach (OMIM#613076). Next generation sequencing recently confirmed this association by the finding of compound heterozygous variants in 19-year-old girl with a strikingly similar phenotype, but this ultra-rare entity remains however unknown from most of the scientific community. MATERIALS AND METHODS: Whole exome sequencing was performed as part of a "diagnostic odyssey" for suspected mitochondrial condition in 2 patients, presenting congenital cataracts, progressive encephalomyopathy and hypotrophy and detected unreported compound heterozygous variants in GFER. RESULTS: Thanks to an international data sharing, we found 2 additional patients carrying compound heterozygous variants in GFER. Reverse phenotyping confirmed the phenotypical similarities between the 4 patients. Together with the first literature reports, the review of these 8 cases from 4 unrelated families enables us to better describe this apparently homogeneous disorder, with the clinical and biological stigmata of mitochondrial disease. CONCLUSION: This report highlights the clinical utility of whole exome sequencing and reverse phenotyping for the diagnosis of ultra-rare diseases and underlines the importance of a broad data sharing for accurate clinical delineation of previously unrecognized entities.

[Influence of genetic factors on the development of target organ lesions in relation to age in diagnosis of arterial hypertension].

AIM: To analyze the impact of polymorphism of a group of genes encoding for endothelial function on the development of target organ lesions in arterial hypertension (AH) in relation to age. SUBJECTS AND METHODS: Six hundred and seventy-two AH patients (mean age 50.6 years; men 67%) were examined. Microalbuminuria (MAU) was estimated. Electrocardiography, echocardiography, and carotid ultrasonography were performed. A control group comprised 184 subjects. Single-nucleotide substitutions genotyping of the Glu298Asp endothelial NO synthase (eNOS), p22phox of NADPH oxidase subunit C242T, and angiotensin II type 1 receptor (ATR1) A1166C gene polymorphisms was conducted by a polymerase chain reaction (PCR) via restriction fragment length polymorphism analysis, and M235T substitution genotyping of the G-6A polymorphism of the angiotensinogen gene was performed by a real-time allele-specific PCR. The impact of the polymorphisms on the development of MAU, left ventricular hypertrophy (LVH), carotid lesion was analyzed in the groups: AH was diagnosed in subjects aged less than 35 years (n = 128) or older. The ultrasound signs of carotid lesion, LVH, and MAU were revealed in 65, 39, and 10.5% of the patients with AH, respectively. RESULTS: The subgroups showed differences in the distribution of polymorphisms of the study genes in relation to age at AH detection. CONCLUSION: In patients with AH diagnosed at less than 35 years of age, pathological changes in the carotid are associated with a G allele of the Glu298Asp eNOS polymorphism (odds ratio (OR) = 2.3; p = 0.016) and with an T allele of the p22phox of NADPH oxidase subunit C242T polymorphism (OR 1.7; p = 0.049). In this age subgroup, LVH was associated with an A allele of the Glu298Asp eNOS polymorphism (OR = 1.9; p = 0.037), MAU was with an A allele of the Glu298Asp eNOS polymorphism (OR = 3.6; p = 0.02) and a C allele of the ATR1 A1166C gene polymorphism (OR = 2.6; p = 0.034).

High incidence of profound biotinidase deficiency detected in newborn screening blood spots in the Somalian population in Minnesota.

Newborns identified with profound biotinidase deficiency (BTD) by the Minnesota Newborn Screening Program (MN NBS) between 1 October 2004 and 30 May 2008 were all from new immigrant groups. Thirty-three positive cases of BTD were identified out of 264 727 infants screened by the Wolf colorimetric system during the period of this study by MN NBS. Five cases of profound BTD (0.1 to <0.6 nmol/min per ml) and 26 cases of partial BTD (0.9 to 2.3 nmol/min per ml) were later confirmed through measurement of serum biotinidase activity. The incidence of combined partial and profound BTD of 1/8540 and that of profound BTD of 1/52 945 in Minnesota are unusually high in comparison with the reported worldwide numbers of 1/61 067 for combined BTD and 1/137 401 for profound BTD. Four out of the 5 cases of profound BTD ascertained in the MN NBS cohort were of Somali ethnic background, and the remaining case was of Asian (Pakistani/Indian) ethnic background. All four Somali patients have the P497S mutation, with one of the four being homozygous for the mutation. The three compound heterozygotes all have a novel mutation (P142T) and two of them have another change (Y428Y) that has never been described. Within the last two decades, Minnesota has become home to an estimated 40 000 Somali immigrants and their children (<1% of the total Minnesota population). New population demographics prompt careful analysis of case cohorts to identify specific groups at risk for rare inborn errors of metabolism.

[Characteristics of moving regime in elderly people].

Wide application of health-improving physical culture can contribute to active life prolongation. Senior people are usually not involved into organized occupations. There is no concept of organization for senior people physical lessons in our days. The most important direction of the considered problem is regulation of physical load. Its value should be optimal, maximum permissible, individual and based on the biological age but not on the calendar one.

Ultra sensitive sensor with enhanced dynamic range for high speed detection of multi-color fluorescence radiation.

This paper describes design of the new ultra sensitive sensor system for fluorescence detection applications. System comprises two units: optical spectra separation unit and detection unit. Optical unit of the sensor performs spatial spectra separation of signal from the laser excited fluorescence, and resulting spectra is collected in the detection part of the system. Optical part is built using diffraction grating as spectra separation element. Detection part comprises 32-channel photomultiplier tube working in single photon counting mode with our 32-channel amplifier. Using single photon detection technique and specific signal processing algorithms for collected data, the proposed system allows to achieve unique combination of characteristics--high sensitivity, high detection speed and wide linearity dynamic range comparing to existing commercial instruments. DNA sequencing experiments with new sensor as detection device, and using two types of lasers (Ar-ion and Nd-YAG) were carried out, yielding sequencing traces which have quality factor of 20 for read lengths as long as 650 base pairs.

Essential fatty acid profiling for routine nutritional assessment unmasks adrenoleukodystrophy in an infant with isovaleric acidaemia.

We report a 16-month-old asymptomatic male with enzyme confirmed isovaleric acidaemia (IVA; isovaleryl-CoA dehydrogenase deficiency; OMIM 243500) who, upon routine nutritional follow-up, presented evidence of peroxisomal dysfunction. The newborn screen (2 days of life) revealed elevated C(5)-carnitine (2.95 µmol/L; cutoff <0.09 µmol/L) and IVA was subsequently confirmed by metabolic profiling and in vitro enzymology. Plasma essential fatty acid (EFA) analysis, assessed to evaluate nutritional status during protein restriction and L: -carnitine supplementation, revealed elevated C(26:0) (5.0 µmol/L; normal <1.3). Subsequently, metabolic profiling and molecular genetic analysis confirmed X-linked adrenoleukodystrophy (XALD). Identification of co-inherited XALD with IVA in this currently asymptomatic patient holds significant treatment ramifications for the proband prior to the onset of neurological sequelae, and critically important counselling implications for this family.

[Influence of polymorphism's of endothelial nitric oxide synthase gene and polymorphism of NADPH oxidase gene on development of complications of arterial hypertension].

The aim of the study was to analyze the prevalence of polymorphism Glu298Asp of endothelial nitric oxide synthase gene and C242T p22 phox polymorphism of NADPH oxidase gene in patients with arterial hypertension (AH) and their influence on AH complications. The study included 272 AH patients, average age 50,7 years. The following analyses were performed: clinical analysis of the blood, general analysis of the urine, lipid spectrum, plasma electrolytes, creatinine, glucose, electrocardiography, echocardioscopy, examination of eye vessels, ultrasound examination of the carotid arteries, determination of microalbuminuria. The polymorphism Glu298Asp of endothelial nitric oxide synthase gene and C242T p22 phox polymorphism of NADPH oxidase gene were detected with two methods: polymerase chain reaction and restrictase reaction. The control group for Glu298Asp polymorphism detection included 102 healthy Russian donors aged 18 to 50 years. Genotypes prevalence in AH patients was as follows: GG 58,8%, GA 32,3%, AA 8,9%, and CC 48,2%, CT 44,9%, TT 6.9%. In the control group: GG 53%, GA 36%, AA 11% and CC 42%, CT 54%, TT 4%. These polymorphisms did not affect the incidence of complications, such as obliterating atherosclerosis of the lower extremity vessels, ischemic heart disease, and acute insufficiency of cerebral circulation, chronic heart failure, left ventricular hypertrophy, microalbuminuria, carotid arteries atherosclerosis.

[Acoustic microscopy application for the evaluation of restorative materials bonding quality. Experimental investigation].

Ultrasound transmission and reflection at the interface between restorative material and tooth tissue have been investigated using experimental flat-parallel models and whole extracted human teeth with restorations. It has been found that in the case of good bonding the ultrasound wave energy practically does not reflect at the cement/dentin interface and propagates into dentin layer. If any microscopic cavity had been formed between cement and dentin, the most part of the acoustic energy would be reflected from the interface between cement and gaseous or liquid contents of that cavity. The results acquired have been used for the interpretation of morphological peculiarities of the adhesive bonding area in visual images, non-destructively obtained in acoustic microscope ultrasound frequency - 50 MHz. The differences discovered could be used as a base for the design and development of new ultrasound methods for the restorative materials bonding evaluation as well as for secondary caries revealing.

Reduction of the false-positive rate in newborn screening by implementation of MS/MS-based second-tier tests: the Mayo Clinic experience (2004-2007).

The continued expansion of newborn screening programmes to include additional conditions increases the responsibility of newborn screening laboratories to provide testing with the highest sensitivity and specificity to allow for identification of affected patients while minimizing the false-positive rate. Some assays and analytes are particularly problematic. Over recent years, our laboratory tried to improve this situation by developing second-tier tests to reduce false-positive results in the screening for congenital adrenal hyperplasia (CAH), tyrosinaemia type I, methylmalonic acidaemias, homocystinuria, and maple syrup urine disease (MSUD). Beginning in 2004, this approach was applied to Mayo's newborn screening programme and resulted in a false-positive rate of 0.09%, a positive predictive value of 41%, and a positive detection rate of 1 affected case in 1672 babies screened.

Clinical, enzymatic and molecular characterization of nine new patients with malonyl-coenzyme A decarboxylase deficiency.

We report nine new patients with malonic aciduria associated with enzyme-confirmed malonyl-CoA decarboxylase (MCD) deficiency in eight. Clinical details were available on eight, and molecular genetic characterization was obtained for nine. As for 15 previously described patients, cardinal clinical manifestations included developmental delay and cardiomyopathy; metabolic perturbations (e.g. acidosis) and seizures, however, were infrequent or not observed in our patients. For all, detection of elevated malonic acid in urine (+/- increased C3DC acylcarnitine by analysis employing tandem mass spectrometry) led to pursuit of enzyme studies. MCD activities (nmol/h PER mg protein) revealed: control (n = 22), 16.2 +/- 1.8 (SEM; range 5.7-46.2); patients (n = 8, assayed in duplicate), 1.7 +/- 0.3 (10% of parallel control; range 0.6-2.8). Molecular characterization by DNA sequence analysis and multiplex ligation-dependent probe amplification revealed nine novel mutations (c.796C>T; p.Gln266X, c.481delC; p.Leu161CysfsX18, c.1367A>C; p.Tyr456Ser, c.1319G>T; p.Ser440Ile, c.1430C>T; p.Ser477Phe, c.899G>T; p.Gly300Val, c.799-1683_949-1293del3128, and two other large genomic deletions comprising exons 1 or the complete gene) and two known mutations in the MLYCD gene. Our findings increase the number of enzyme-confirmed MCD-deficient patients by >50%, and expand our understanding of the phenotypic and molecular heterogeneity of this rare disorder.

[Epidemiologic situation of arterial hypertension on industrial enterprise].

Arterial hypertension is widely prevalent disease (38.1% in Russia) and increases death rate with coronary heart disease 3-fold, with stroke--6-fold. Multiple prospective studies proved that opportune diagnosis of arterial hypertension and other risk factors, as well as their sufficient correction considerably lower risk of occurrence and unfavorable outcomes of arterial hypertension complications. With this, organization of prophylactic programs on outpatient basis seems extremely important.

Expression of urokinase plasminogen activator and receptor in conjunction with the ets family and AP-1 complex transcription factors in high grade prostate cancers.

Expression of the urokinase plasminogen activator (uPA) and its receptor (uPAR) correlates with tumour cell invasiveness and helps to determine the prognosis of prostate and other cancers. The purpose of this study was to establish in prostate cancer, the ets family and AP-1 complex transcription factors that might activate the inducible AP-1 and AP-1/PEA3 elements of the uPA enhancer. uPA and uPAR were expressed preferentially in adenocarcinoma cells, but not the stroma of high grade prostate cancers. The ets family paralogues Fli-1 and Elf-1 were also highly expressed in adenocarcinoma cells of the majority of cancers, while Erg 1,2 and Ets-2 were expressed in a minority of cancers and Elk-1, PEA3 and PU.1 were minimally expressed. A minority of cancers expressed high levels of cytoplasmic and/or nuclear c-Jun and c-Fos transcription factors. We speculate as to the molecular basis for such expression.

Frequency analysis of HLA-DQA1 and HLA-DQB1 gene alleles and susceptibility to type 1 diabetes mellitus in Russian patients.

The HLA-DQA1 and DQB1 genes have recently been recognized to be strong genetic markers of susceptibility to type 1 (insulin-dependent) diabetes mellitus. The Arg52 DQA1 and non-Asp57 DQB1 alleles of these genes correlate with the disease predisposition and the Asp57 DQB1 and non-Arg52 DQA1 alleles with disease protection. We investigated 113 patients with type 1 diabetes and 121 healthy subjects from the Russian population of Moscow using DNA amplification and dot-blot hybridization with sequence-specific oligonucleotides (SSO). Using conventional statistical methods we confirmed previous observations indicating the important role of the above-mentioned amino acid residues in susceptibility and resistance to type 1 diabetes. Relative risk values for all alleles and absolute risk for carriers of most predisposing allele combinations were calculated. The absolute risk for carriers of DQA1 and DQB1 gene alleles allowing for the formation of four possible 'diabetogenic' heterodimers on the surface of immunocompetent cells, regardless of the type of coding (cis or trans), was 2.54%, which is 13 times greater than the background risk for the Russian population--0.2% up to 30 years of age.

[Analysis of the distribution of alleles of four hypervariable tandem repeats among unrelated Russian individuals living in Moscow, using the polymerase chain reaction]. / Analiz racpredeleniia allelei chetyrekh gipervariabel'nykh tandemnykh povtorov sredi nerodstvennykh predstavitelei russkoi natsii, prozhivaiushchikh v Moskve, s pomoshch'iu polimeraznoi tsepnoi reaktsii.

Allele frequencies of four VNTR regions (loci D1S80, D17S30, APOB and IGHJ) were determined in 120 unrelated Russian individuals living in Moscow. The high level of length polymorphism was discovered among alleles of these VNTRs. The genotype distribution of these hypervariable regions was established on the basis of experimental data. The comparative analysis showed the likeness between the allele distributions of these VNTRs among Russians and other groups of Caucasians living in Europe and North America.

[Use of the polymerase chain reaction for typing allelic variants of the human HLA-DQA1 by hybridization with oligonucleotide probes, specific for specific alleles]. / Ispol'zovanie polimeraznoi tsepnoi reaktsii dlia tipirovaniia allel'nykh variantov gena HLA-DQA1 cheloveka po gibridizatsii s oligonukleotidnymi zondami spetsifichenymi k opredelennym alleliam.

Class II HLA molecules are the most useful markers for susceptibility to different autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM) and rheumatoid arthritis (RA). Polymerase chain reaction and hybridization with a set of allele-specific oligonucleotide have been used for analysis of allelic sequence variation. The analysis of frequencies of HLA-DQA1 alleles among 10 patients of the russian population revealed a uneven distribution. We have developed a method for preparing non-radioactive oligonucleotide probes with terminal deoxynucleotidyl transferase and Bio-11-dUTP. Comparison of biotinylated and 32P-labeled hybridization probes gave the same sensitivity for HLA-DQA1 typing of amplified DNA. Amplification of the HLA-DQA1 gene has been successful on 10 pg of total DNA. This amount of DNA is close to the amount of DNA in a single cell. Alternatively, HLA-DQA1 typing could be based on the analysis of buccal cells of saliva that would avoid the problem of individuals who object to giving blood samples.